ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms

Abstract

Renal ischemia reperfusion (IR) injury is a prevalent inflammatory nephropathy in surgeries such as renal transplantation or partial nephrectomy, damaging renal function through inducing inflammation and cell death in renal tubules. Mesenchymal stromal/stem cell (MSC)-based therapies, common treatments to attenuate inflammation in IR diseases, fail to exhibit satisfying effects on cell death in renal IR. In this study, we prepared MSC-derived exosome mimetics (EMs) carrying the mammalian target of the rapamycin (mTOR) agonist to protect kidneys in proinflammatory environments under IR conditions. The thioketal-modified EMs carried the mTOR agonist and bioactive molecules in MSCs and responsively released them in kidney IR areas. MSC-derived EMs and mTOR agonists protected kidneys synergistically from IR through alleviating inflammation, apoptosis, and ferroptosis. The current study indicates that MSC-TK-MHY1485 EMs (MTM-EM) are promising therapeutic biomaterials for renal IR injury.